The Chitosan/Agarose/NanoHA Bone Scaffold-Induced M2 Macrophage Polarization and Its Effect on Osteogenic Differentiation In Vitro

Abstract

Chronic immune response to bone implant may lead to delayed healing and its failure. Thus, newly developed biomaterials should be characterized by high biocompatibility. Moreover, it is well known that macrophages play a crucial role in the controlling of biomaterial-induced inflammatory response. Immune cells synthesize also a great amount of signaling molecules that regulate cell differentiation and tissue remodeling. Non-activated macrophages (M0) may be activated (polarized) into two main types of macrophage phenotype: proinflammatory type 1 macrophages (M1) and anti-inflammatory type 2 macrophages (M2). The aim of the present study was to assess the influence of the newly developed chitosan/agarose/nanohydroxyapatite bone scaffold (Polish Patent) on the macrophage polarization and osteogenic differentiation. Obtained results showed that macrophages cultured on the surface of the biomaterial released an elevated level of anti-inflammatory cytokines (interleukin-4, -10, -13, transforming growth factor-beta), which is typical of the M2 phenotype. Moreover, an evaluation of cell morphology confirmed M2 polarization of the macrophages on the surface of the bone scaffold. Importantly, in this study, it was demonstrated that the co-culture of macrophages-seeded biomaterial with bone marrow-derived stem cells (BMDSCs) or human osteoblasts (hFOB 1.19) enhanced their osteogenic ability, confirming the immunomodulatory effect of the macrophages on the osteogenic differentiation process. Thus, it was proved that the developed biomaterial carries a low risk of inflammatory response and induces macrophage polarization into the M2 phenotype with osteopromotive properties, which makes it a promising bone scaffold for regenerative medicine applications.

High proportion strontium-doped micro-arc oxidation coatings enhance early osseointegration of titanium in osteoporosis by anti-oxidative stress pathway

“…In our study, we found that the macrophages in the high Sr groups (especially Sr100%) exhibited larger cell surface area and more pseudopodia ( Fig. 4 A), which was similar to the cell morphology of M2 macrophage described by Kazimierczak et al [ 62 ]. This further confirms that the high Sr specimens significantly increase the polarization of macrophages from M0 to M2 as well as the expression of the various anti-inflammatory genes/factors (IL10 & IL1ra; Fig.…”

Application Progress of Modified Chitosan and Its Composite Biomaterials for Bone Tissue Engineering

“…After biomaterial implantation, several factors have a significant impact on bone tissue repair, inter alia macrophage–osteoblast cross-talk, soluble environmental factors, and surface properties of the implant [ 37 ]. The success of biomaterial implantation depends highly on the implant’s macrophage polarization [ 38 ]. Macrophages are known to be involved in the in vivo biodegradation of resorbable polymers through the release of reactive oxygen intermediates, enzymes, and acids [ 39 ].…”

Translating Material Science into Bone Regenerative Medicine Applications: State-of-The Art Methods and Protocols

“…They can proliferate and differentiate into osteoblasts upon appropriate stimuli. MSCs isolated from bone marrow are regarded as the gold standard [ 14 , 53 , 55 , 57 , 67 , 68 , 73 , 76 , 77 , 79 , 83 , 91 , 94 , 98 , 107 , 108 , 109 ]. MSC-like cells isolated from the stromal vascular fraction of the adipose tissue, namely, adipose-derived stem cells, ASC, are seldom used in selected applications [ 2 , 65 , 72 , 82 , 89 , 104 , 109 , 110 , 111 , 112 ].…”

“…In the vast majority of papers in the literature, the expression levels of one or more genes associated with osteoblast differentiation are usually evaluated by quantitative real-time PCR (qRT-PCR) and/or Western blot and/or immunofluorescence analysis and/or ELISA assay [ 14 , 55 , 57 , 58 , 60 , 62 , 64 , 65 , 68 , 69 , 70 , 72 , 73 , 76 , 77 , 79 , 80 , 82 , 83 , 84 , 86 , 87 , 89 , 90 , 91 , 94 , 96 , 98 , 100 , 108 , 109 , 113 ]. Table 3 reports the most representative osteogenic genes usually analyzed.…”